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Monocyte chemoattractant protein 1 and macrophage cyclooxygenase 2 expression in colonic adenoma
  1. S Tanaka,
  2. A Tatsuguchi,
  3. S Futagami,
  4. K Gudis,
  5. K Wada,
  6. T Seo,
  7. K Mitsui,
  8. M Yonezawa,
  9. K Nagata,
  10. S Fujimori,
  11. T Tsukui,
  12. T Kishida,
  13. C Sakamoto
  1. Third Department of Internal Medicine, Nippon Medical School, Tokyo, Japan
  1. Correspondence to:
    Professor C Sakamoto
    Third Department of Internal Medicine, Nippon Medical School, 1-1-5, Sendagi, Bunkyo-ku, Tokyo, 113-8603, Japan; choitsu{at}


Background and aims: Cyclooxygenase 2 (COX-2) expression in subepithelial macrophages of colorectal adenoma has been suggested as the first in a series of steps leading to colorectal tumorigenesis. We tested the hypothesis that chemokines released from human colorectal adenoma epithelium might be involved in COX-2 expression in macrophages of the lamina propria.

Methods: Endoscopic samples of sporadic colorectal adenomas were tested by enzyme linked immunosorbent assay for chemokines involved in macrophage chemotaxis. Localisation of adenoma macrophage chemoattractant protein 1 (MCP-1) and COX-2 were determined by immunohistochemistry. The effects of MCP-1, in the presence or absence of celecoxib, on COX-2 expression, and prostaglandin (PG) E2 and vascular endothelial growth factor (VEGF) release, were examined in human macrophages isolated from peripheral blood.

Results: MCP-1 levels were markedly higher in adenoma with mild-moderate dysplasia (129.7 (19.9) pg/mg protein) and severe dysplasia (227.9 (35.4) pg/mg protein) than in normal colonic mucosa (55.8 (4.2) pg/mg protein). Other chemokine levels, macrophage inflammatory proteins (MIP)-1α and MIP-1β, and the chemokine regulated on activation of normal T cell expressed and secreted (RANTES) did not vary significantly between adenoma and normal mucosa. MCP-1 levels in both adenoma and normal colonic mucosa increased significantly three hours after tissue cultivation in vitro. MCP-1 immunoreactivity was restricted to the adenoma epithelium, with no reactivity seen in adjacent normal epithelial cells. MCP-1 stimulated COX-2 expression and PGE2 and VEGF release in human macrophages. Celecoxib, a selective COX-2 inhibitor, inhibited MCP-1-induced PGE2 and VEGF release in macrophages. Addition of exogenous PGE2 reversed this inhibitory effect on VEGF release, suggesting that MCP-1 in adenoma epithelial cells might be involved in COX-2 expression and subsequent macrophage activation.

Conclusions: MCP-1 in colorectal adenoma epithelial cells might be involved in macrophage migration and COX-2 expression, leading to the subsequent development of colonic adenoma.

  • COX-2, cyclooxygenase 2
  • MCP-1, macrophage chemoattractant protein
  • PG, prostaglandin
  • VEGF, vascular endothelial growth factor
  • RANTES, regulated on activation of normal T cell expressed and secreted
  • ELISA, enzyme linked immunosorbent assay
  • MIP, macrophage inflammatory protein
  • NSAIDs, non-steroidal anti-inflammatory drugs
  • FAP, familial adenomatous polyposis
  • H&E, haematoxylin and eosin
  • PBS, phosphate buffered saline
  • EDTA, ethylenediaminetetraacetic acid
  • PMSF, phenylmethylsulfonyl fluoride
  • FITC, fluorescein isothiocyanate
  • PBMC, peripheral blood mononuclear cells
  • FCS, fetal calf serum
  • LPS, lipopolysaccharide
  • CHAPS, 3-[(3,cholamidopropyl)-dimethylammonio]-l-propane-sulfonate
  • cyclooxygenase
  • macrophage chemoattractant protein
  • adenoma
  • macrophage

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  • Conflict of interest: None declared.